Abstract
Background: Cell-free DNA (cfDNA) sequencing has emerged as an effective laboratory method for rapid and noninvasive diagnosis in prenatal screening testing, organ transplant rejection screening, and oncology liquid biopsies. Methods: Here we report our experience using next-generation sequencing (NGS) for detection of microbial cfDNA in a cohort of ten immunocompromised patients with febrile neutropenia or deep-seated infection. Results: Among five hematological malignancy patients, for whom a microbiological diagnosis was established, pathogen identification by cfDNA NGS demonstrated 100% positive agreement with conventional diagnostic laboratory methods. Further, cfDNA identified the etiological agent in two patients with culture negative sepsis who had undergone hematopoietic stem cell transplant. Conclusion: These data support the clinical utility of measurement of microbial cfDNA sequencing from peripheral blood for rapid noninvasive diagnosis of infections in immunocompromised hosts. Larger studies are needed.
Highlights
Infections are a leading cause of morbidity and mortality among immunocompromised individuals[1,2,3,4]
All febrile patients had blood cultures collected within 24 hours of plasma sample collection for next-generation sequencing (NGS)
Among patients with hematological malignancy in whom a microbiological diagnosis was established (n=5), Cell-free DNA (cfDNA) NGS testing correlated with other methods in all cases (100% sensitivity)
Summary
Infections are a leading cause of morbidity and mortality among immunocompromised individuals[1,2,3,4]. Infection is a leading cause of non-relapse mortality among hematopoietic cell transplantation (HCT) recipients[6]. The incidence of bacteremia[7,8,9] and double-stranded DNA viral reactivation[10] is higher than 40% and 90%, respectively, within the first 100 days post-transplant. Cell-free DNA (cfDNA) sequencing has emerged as an effective laboratory method for rapid and noninvasive diagnosis in prenatal screening testing, organ transplant rejection screening, and oncology liquid biopsies. Methods: Here we report our experience using next-generation sequencing (NGS) for detection of microbial cfDNA in a cohort of ten immunocompromised patients with febrile neutropenia or deep-seated infection. Conclusion: These data support the clinical utility of measurement of microbial cfDNA sequencing from peripheral blood for rapid noninvasive diagnosis of infections in immunocompromised hosts.
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